The presence of dogs with selective IgA deficiency has been documented in a large Beagle breeding kennel. This is an unique spontaneous animal model with clinical and immunologic findings similar to that of selective IgA deficiency in man, the most common human primary immunodeficiency. The disease in the dog is characterized by chronic, recurrent respiratory infections, dermatitis, and possibly gastrointestinal infections low concentrations of serum IgA, and normal concentrations of IgG and IgM; normal T cell function as measured by lymphocyte transformation tests; the presence of autoantibodies; and a defect in the terminal differentiation of IgA B cells into IgA secreting plasma cells. This animal model may prove useful in addressing some of the important questions which remain to be answered concerning human selective IgA deficiency. The underlying immunologic defect in man is not fully defined nor has the mode of inheritance been well defined. Another current point of controversy is the role of a "true" IgA deficiency and low IgA concentrations in the manifestation of clinical disease. These specific aims of this proposal are: 1. To develop a breeding colony of IgA deficient dogs from animals we have already identified at the kennel. 2. To define the mode of interitance of selective IgA deficiency in these dogs. 3. To determine the cellular defect(s) in selective IgA deficiency in this population. 4. To define the relationship of selective IgA deficiency, and the severity of the deficiency, to clinical infections of the respiratory tract, gastrointestinal tract and skin. 5. To define the relationship of selective IgA deficiency, and the severity of the deficiency, to atopic and autoimmune disease. 6. To develop and evaluate modes of therapeutic intervention in selective IgA deficiency.